Fig. 41.14 ). GnRH is produced as a larger prohormone and, as part of its processing to a decapeptide, is modified with a cyclized glutamine (pyro-Glu) at its N-terminus and an amidated C-terminus.
GnRH is released in a pulsatile manner (
Fig. 41.15 ), and both the pulsatile secretion and the frequency of the pulses have important effects on the gonadotrope. Continuous infusion of GnRH downregulates the GnRH receptor, thereby resulting in a decrease in FSH and LH secretion. In contrast, pulsatile secretion does not desensitize the gonadotrope to GnRH, and FSH and LH secretion is normal. At a frequency of one pulse per hour, GnRH preferentially increases LH secretion (
Fig. 41.16 ). At a slower frequency of one pulse per 3 hours, GnRH preferentially increases FSH secretion. Gonadotropins increase sex steroid synthesis (see
Fig. 41.14 ). In men, testosterone and estrogen negatively feed back at the level of the pituitary and the hypothalamus.
Ca++, PKC, other pathways? SlowFast GnRH (+) pulses GnRH pulses LH synthesis and secretion FSH synthesis and secretion FSHLH PKA Inhibin Pulsatile release of GnRH at median eminence PubertyCNS Opioids Stress Prolactin (−)Sex steroids GnRH neurons inputs (+) (−) (−) GnRH Sex steroids GnRH receptor FSH receptorLH receptor Pituitary gonadotrope Gonadal cell types Steroidogenesis Gametogenesis •Fig. 41.14 Hypothalamic-pituitary-gonadalaxis.FSH,follicle-stimulatinghormone;GnRH,gonadotropin-releasinghormone;LH,luteinizinghormone.(ModifiedfromPorterfieldSP,WhiteBA.Endocrine
Physiology. 3rded.Philadelphia:Mosby;2007.)
Exogenous progesterone also inhibits gonadotropin function in men and has been considered as a possible component of a male contraceptive pill. Additionally, inhibin negatively feeds back selectively on FSH secretion in men and women. In women, progesterone and testosterone negatively feed back on gonadotropic function at the level of the hypothalamus and pituitary. At low doses, estrogen also exerts negative feedback on FSH and LH secretion. However, high estrogen levels maintained for 3 days cause a surge in LH and to a lesser extent FSH secretion. This positive feedback, which is critical in promoting ovulation, is observed at the hypothalamus and pituitary. At the hypothalamus, GnRH pulse amplitude and frequency increase. At the pituitary, high estrogen levels greatly increase the sensitivity of the gonadotrope to GnRH, both by increasing GnRH receptor levels and by enhancing postreceptor signaling (see
The Somatotrope
The somatotrope produces GH (somatotropin) and is part of the hypothalamic-pituitary-liver axis (
Fig. 41.17 ). A major target of GH is the liver, where it stimulates production of insulinlike growth factor (IGF)-I. GH is a 191–amino acid protein that is similar to PRL and human placental lactogen (hPL); accordingly there is some overlap in activity among these hormones. Multiple forms of GH 746 SECTION8Berne & Levy Physiology 1.8 1.2 0.6 0 12 10 8 6 1200 1300 1400 1500 1600 Hours GnRH(pg/10 min) LH(ng/mL)